Although iron and copper are co-ordinately regulated in living cells, the homeostatic effects of each of these metals on the other remain unknown. Here, we show the function of AfMac1, a transcriptional activator of the copper and iron regulons of Aspergillus fumigatus, on the interaction between iron and copper. In addition to the copper-specific AfMac1-binding motif 5′-TGTGCTCA-3′ found in the promoter region of ctrC, the iron-specific AfMac1-binding motif 5′-AT(C/G)NN(A/T)T(A/C)-3′ was identified in the iron regulon but not in the copper regulon by ChIP sequence analysis. Furthermore, mutation of the AfMac1-binding motif of sit1 eliminated AfMac1-mediated sit1 up-regulation. Interestingly, the regulation of gene expression in the iron regulon by AfMac1 was not affected by copper and vice versa. AfMac1 localized to the nucleus under iron- or copper-depleted conditions, and AfMac1 was mostly detected in the cytoplasm under iron- or copper-replete conditions. Taken together, these results suggest that A. fumigatus independently regulates iron and copper homeostasis in a manner that involves AfMac1 and mutual interactions.
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Cover Image
Cover Image
In this issue of the Biochemical Journal, Tong et al. report how a sesquiterpene synthase generates eudesmane-type sesquiterpene diols in Tripterygium wilfordii and which residues are important for cyclization. The cover image shows the flower of T. wilfordii and the structure of cryptomeridiol synthase. The background depicts ancient Chinese text that recorded the medicinal benefits of T. wilfordii and the engineered manipulation in yeast to enhance the production of the eudesmane diol cryptomeridiol. For further details, see pages 2713–2725. Image kindly provided by Wei Gao (Capital Medical University, Beijing).
A copper transcription factor, AfMac1, regulates both iron and copper homeostasis in the opportunistic fungal pathogen Aspergillus fumigatus
Yong-Sung Park, Suzie Kang, Hyewon Seo, Cheol-Won Yun; A copper transcription factor, AfMac1, regulates both iron and copper homeostasis in the opportunistic fungal pathogen Aspergillus fumigatus. Biochem J 14 September 2018; 475 (17): 2831–2845. doi: https://doi.org/10.1042/BCJ20180399
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